Branchio-Oto-Renal Syndrome (BOR) is an autosomal dominant disorder which consists of external, middle and inner ear malformations, branchial cleft sinuses, cervical fistulas, mixed hearing loss and renal anomalies. Variable clinical expression between families suggest that multiple gene loci are involved in causing the disease. However, the cause of genetic heterogeneity and clinical variability cannot be resolved until the gene(s) causing BOR syndrome is localized on a chromosome through linkage studies. Thus, the main objective of this genetic study is to map the BOR gene through linkage studies using DNA markers. Initially, four clinically well characterized families will be studied. The DNA from informative individuals will be amplified by Polymerase Chain Reaction using primers near to highly polymorphic dinucleotide repeats. These polymorphisms are distributed widely throughout the human genome. Linkage analysis between these markers and BOR will be done using the LINKAGE (Version 5.04) program. Additional families will be ascertained and tested for linkage with the genes localized in the initial four families. The possibility of genetic heterogeneity will be explored using the program HOMOG and unlinked families will be put through another round of genome searching to determine location of newly discovered genes. Clinical differences between families will be analyzed to determine to what degree they are correlated with different linkage groups. The BOR syndrome results in branchial, auditory, and renal, abnormalities in affected individuals and poses serious health problems. Identification of the BOR gene(s) is the first and foremost step to a more comprehensive understanding of the pathogenesis and etiology of this syndrome. Finding the gene(s) through linkage studies will lay the foundation for further research to isolate and clone such genes for effective treatment and genetic counseling.